Placenta accreta outcomes and risk factors in a referral hospital in north of Iran: A case control study

Abstract Background Placenta accreta syndrome (PAS) may led to heavy blood loss and maternal death. Here we analyzed the main risk factors of PAS+ pregnancies and its complications in a referral hospital in the north of Iran. Methods In a case control study, all pregnant women with PAS referred to our department during 2016 till 2021 were enrolled and divided in two groups case (PAS+) and control (PAS−) based on preoperative imaging, intraoperative findings, and pathological reports. The sociodemographic features and neonatal‐maternal outcomes also were recorded. Results The most frequent reason for cesarean (C/S) was repeated C/S (62.9%, 56/89). A significant difference showed up in the time lag between previous C/S and the present delivery (p < 0.001) which shows that when the time distance is longer, the risk of PAS rises (OR: 1.01 [95% CI: 1.003−1.017]). Also, a positive history of prior abortion and elective type of previous C/S were related to PAS+ pregnancies. Our other finding showed that PAS+ pregnancies will end in lower gestational age and have a longer duration of operation and hospitalization, heavy blood transfusion, and hysterectomy. Also, PAS+ pregnancies were not related to poor neonatal outcomes. Conclusions It seems that, in addition to repeated C/S as a strong risk factor, previous abortion is a forgotten key which leads to incomplete evacuation or damage the endometrial‐myometrial layers.


| INTRODUCTION
Placenta accreta syndrome (PAS) is a serious life-threatening obstetric disorder which is characterized by placental adhesion to the uterine wall during labor. 1 According to the depth of placental invasion into the myometrium and the adjusted organs, PAS divided to placenta accreta, increta, and percreta. 2Nowadays, due to the increasing rate of cesarean delivery, the incidence rate of PAS is rising worldwide. 3,4In the same way, in a survey in Iran in 2018, the rate of cesarean sections was rising and reported around 50%-60% of total deliveries. 5Also, in another study in Iran on 2021, Kasraeian et al. 6 revealed a rate of 1/263 cases for PAS + pregnancies which were one of the most important high reported prevalence of PAS.
PAS is usually diagnosed using sonography with 87% sensitivity and 98% specificity. 7Other diagnostic modalities are magnetic resonance imaging (MRI) and histopathological evaluation. 8[5][6][7][8] In PAS + pregnancies, due to the high amount of blood loss, it might be necessary to change the treatment plan to cesarean-hysterectomy (a C/S followed by the hysterectomy). 8Obstetricians prefer to terminate such pregnancies earlier in tertiary centers, and in some cases, it requires several surgical specialists in the surgery setting and it also may need to massive blood transfusion. 7,8spite the strong relationship between previous C/S and PAS, all of repeated C/S are not involved with, and on the other hand, there are some reports of primiparus pregnancies complicated with PAS. 9 So here we studied the other risk factors of PAS + and the maternal and neonatal outcomes.

| Study design
This is a case control study from March 2016 to 2021.

| Study population
All the pregnant women with a prior cesarean section (PAS− and PAS+ confirmed with preoperative imaging, intraoperative findings, and histopathological reports) referred to obstetrics and gynecology center at Rash Hospital.

| Sample size and sampling methods
Sample size was calculated through the following formula and the data of Farquhar et al. 8 with a confidence interval of 95%, a margin of error of 0.05, and 80% power of the study.
( ) Sampling done using convenient sampling methods.
Inclusion criteria includes preoperative ultrasonographic or MRI evidence of PAS, intraoperative findings, postoperative pathological sample report with loss of the layer interfaces between the placenta decidua and myometrium (Nitabuch layer).Patients with no ultrasonography of the placenta excluded from the survey.

| Study groups
The case group (PAS+) consisted of all pregnant women placenta accrete syndrome and the control group (PAS−) was consisted of pregnant women without PAS.Both the groups were matched for maternal age, parity, and gestational age (Figure 1).Using a data collection sheet, all variables of the study were recorded.The checklist contained of two main sections: The first section: sociodemographic characteristics; the second section: maternal and neonatal outcomes.

| Data analysis
The findings were statistically analyzed using SPSS software v. 22.0 (SPSS Inc.).The frequency and percentage were used to report the qualitative results.For the quantitative data, mean and standard deviation were used.To comparison the variables, independent T-test, χ 2 , and fisher exact test were used.Mann-Whitney test and Wilcoxon test used in nonparametric results.p < 0.05 is considered statistically significant.

| RESULTS
A total number of 267 pregnant women with previous cesarean were evaluatedand 89 pregnant women with PAS + were allocated in the case group and 178 women without PAS (PAS -) allocated in the control group.
The age ranged from 19 to 44 years with a mean age of 32.8 ± 4.8 years in the case group and 26.9 ± 2.9 years in the control group (p > 0.05).The distribution of demographic characteristics in the two study groups is shown in Table 1.Sociodemographic variables are comparable between study groups except for history of abortion (Table 1).
The most frequent reason for cesarean delivery was repeated C/S in both the study groups.
The time lag between previous C/S and the present delivery is significantly longer in the case group as compared to control group (p < 0.001).The details are shown in Table 2.The mean gestational age at the time of delivery was 35.1 ± 2.9 and 37.7 ± 1.1 weeks in the case and control groups, respectively (p < 0.001).It shows that in PAS + pregnancies, the time of delivery is earlier.The average duration of hospitalization was 3.5 ± 1.9 days in the case group which was longer than the control group (p < 0.001).
In the same way, operation time was longer in the case group (74.42 ± 29.4 vs. 55.08 ± 13.09 min) (p < 0.001).The mean blood loss in the case group was 2544 mL which was significantly more than the control group (p < 0.001).Blood transfusion happen in 53.93% of case and 21.9% of control patients (p < 0.001).Cesarean hysterectomy performed in 39 mothers in the case group and only one mother in control group (p < 0.001).Furthermore, ICU admission was in all patients in the case group and only 6.17% of the control group (p < 0.001).Neonatal characteristics did not differ between the two study groups (Tables 2 and 3).The locations of the PAS within the uterine cavity are based on the preoperative imaging studies or preoperative findings are shown in Table 4.
Table 5 shows multivariate logistic regression on the different risk factors associated with PAS+ pregnancies.The analysis shows a significant relationship between PAS+ pregnancies and a history of prior abortion and type of cesarean section (Table 5).

| DISCUSSION
PAS is a life threatening situation which leads to severe maternal morbidities and mortalities specially due to the high amount of blood loss.Of course, early diagnosis can be a golden key to save such mother's life and in pregnancies with more risk factors of PAS, such as placenta previa and scarred uterus, it should be considered as soon as possible.Our results showed the significance of PAS + pregnancies management due to the probable morbidities such as heavy blood loss, ICU admission, prolonged hospitalization, and permanent infertility due to hysterectomy.
The most famous hypothesis for the PAS etiology is the endometrial-myometrial interface defect at the previous C/S scar or any other incisions the endometrium which results in abnormal decidualization and deep anchoring of chorionic villi and trophoblast infiltration which can invade the myometriuma and serosa layer.
A fertilized egg needs an environment of both oxygen and collagen for implantation.Because the uterine scar possesses the both, during a repested pregnancy, embryos will be implanted at the incision site.Also, there are several parts of discontinuity and thinning in a repeated C/S uterine results in a poor growth of the tunica intima and a weaken myometrium.
In fact, the scar of hysterotomy may damage the terminal layer on the implantation site, and therefore, in the next pregnancies placenta will be directly in touch with myometrium. 10,11 the same way, our results showed that all patients had a positive history of previous C/S, but, there were no relationship between the number of previous C/S and the risk of PAS.Despite our results, in another study on evaluation of PAS during 4 decades on 2013, the only variable which differ statistically significant was the number of previous C/S. 12Along with our results, Erfani et al. 10 showed a higher rate of previous C/S in PAS + pregnancies (89.9% vs. 46.8%; p < 0.001).We found no relationship between maternal age and the risk of PAS, maybe due to the matching process in include patients in the control group.In another case control study, Farquhar et al. 8 showed that in pregnant women older than 40 years old, the risk of PAS is higher than those younger than 30 years old.Also, Meng et al. 13 showed that with rising in maternal age, the risk of PAS rises with no relationship to the history of C/S.
Among other demographic features, there were a significant relationship between previous elective C/S, the long inter pregnancies interval, positive history of placenta previa and a history of abortion.Similar to our results, there are several studies which declare that placenta previa is an independent risk factor for placenta accrete most likely due to the overlap of their common risk factors and underlying causes. 11,12,14Also, due to the hematoma or remnant placental tissue within the myometrium layer, a positive history of abortion may be a risk factor of a weak point for future PAS. 15 There are some studies declared that with a short interval between the previous C/S and the present pregnancy, the risk of PAS rises 16,17 which may be related to the incomplete healing of the scar of the previous incision.But we found the opposite, and in short term inter pregnancies interval, PAS happened more frequent.
Abdelrahman et al. 18 declared that despite the overall belief, there is no relationship between the time lag between the two C/S and PAS.
Our other findings showed the more frequent type of previous

T A B L E 4
The locations of the PAS within the uterine cavity base on the preoperative imaging studies or preoperative findings.

PAS location n (%)
In the lower uterine segment 38 (42.7%) On anterior uterine wall 51 (57.3%) On the posterior uterine wall 0 (0%) On fundal region of the uterine cavity.0 (0%) Abbreviation: PAS, placenta accreta syndrome.elective C/S, lower segment has a thick myometrium and healing with fibrosis will led to a defect named "Niche" which has a high risk of PAS in implantation of ovum on this sit.[12][13] Our study showed that PAS + pregnancies will end in lower gestational age, longer duration of operation and hospitalization, heavy blood transfusion, and hysterectomy.Along with our results, Shi et al. 14 showed that elective C/S has higher rate in PAS+ pregnancies with lower gestational age.Farquhar et al. 8 showed that PAS + pregnancies had more positive history of C/S and resulted in ICU admission and hysterectomy.Erfani et al. 10 resulted a higher amount of blood loss and transfusion in PAS + pregnancies.In a 5-years survey, Kasraeian et al. 6 resulted that the mean amount of blood loss during PAS + C/S was 2.5 L and the average amount of blood transfusion was two packed cell.About the neonatal results, there were no significant relationship between PAS + pregnancies and poor neonatal outcomes.

| CONCLUSION
Accreta syndrome is a life threatening situation which may led to heavy blood loss and maternal death.Our findings showed that in addition to repeated C/S as a strong risk factor, previous abortion is a forgotten key which may become underestimated as a major clue.In our country, due to the culture and religious beliefs, abortion is not legal, so, there are a high number of illegal abortion which leads to incomplete evacuation or damage the endometrial-myometrial layers.
It seems that government should consider novel solutions to decrease such abortions.The other important risk factor in our survey was elective C/S which has a high rate and must be decreased through to encourage primigravide mothers for normal vaginal delivery and avoid of C/S with no medical criteria.

1
Comparison of sociodemographic features between the case and control groups conducted Rasht Hospital, Iran, 2016-2021.
Different types of PAS (based on pathology report.PAS, placenta accreta syndrome.
T A B L E 2 Comparison of prior cesarean section features between case and control groups conducted at Rasht Hospital, Iran, 2016-2021.
C/S was elective surgery.It has been discussed that on emergent C/S which mostly happens during labor phase, proper dilation of lower segment presents a thin uterine wall and a low site incision which leads to a good prognosis for no PAS in future.On the other hand, in T A B L E 3 Comparison of neonatal and maternal outcomes between the two study groups.
T A B L E 5